1. Field of the Invention
The present invention relates to techniques in the field of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). The present invention also relates to techniques for measuring the spatial distribution of the electrical properties of substances such as electrolyte solutions, the tissues of a living body and human tissues by the use of MRI or MRS. The present invention relates also to techniques for measuring the spatial distributions of the currents within these substances.
2. Description of the Prior Art
Magnetic resonance signals are high-frequency signals, typically on the order of microvolts, which have weak frequencies produced by the precession of atomic nuclei (spins) in a static magnetic field. The frequency of the precession is determined by the magnetic field strength and the type of nucleus in question. The spins are aligned by the homogenous static magnetic field, and are excited by the application of an RF field, with the resulting magnetic resonance signals being detected as a voltage with a resonant coil (antenna).
An MR image is abbreviated MRI, and the method for acquiring it is called MR imaging which is abbreviated MRI. Further, MR spectral curve is referred to as an MR spectrum which is abbreviated MRS, and the acquisition of it or the method for acquiring it is called MR spectroscopy, which is abbreviated MRS.
Since R. Damadian found in the early 1970s that the spin-lattice relaxation time T1 and the spin-spin relaxation time T2 vary with tissues significantly, and tumorous tissues have extremely longer relaxation times than normal tissues (R. Damadian, xe2x80x9cTissue detection by nuclear magnetic resonance.xe2x80x9d Science vol. 171: pp. 1151-1153, published in 1971), the relaxation times T1 and T2 have been recognized as very important parameters in developing and designing magnetic resonance imaging systems and obtaining and evaluating magnetic resonance images and spectra.
The relaxation time T1 is the time constant required for the spins excited in a static magnetic field to return to their initial state in which they can be excited again. Accordingly, if T1 of the tissues of a living body or the like (examination subject) is particularly long, then a correspondingly longer time is needed for obtaining the magnetic resonance signals by repeating the excitation, returning the spins to the initial state, and for obtaining MRI or MRS by performing calculations such as two-dimensional Fourier transform or one-dimensional Fourier transform with a computer. In case of a clinical MRI apparatus, the patient, who is not allowed to move during the image pickup, is more burdened. Further, the number of patients who can be imaged over a given time is decreased. Accordingly, it is generally considered better for T1 to be shorter.
The relaxation time T2 is the time constant from a time when many spins are excited in resonance with the RF field (i.e., the field having the same frequency as the frequency of the precession relative to the magnetic flux density of the static magnetic field around the spins), so that the phases of the precessions are uniform and can be detected macroscopically as an induced electromotive force by an external resonance coil, to when the phases become irregular and non-uniform, so that the spins cannot detected. Accordingly, in order to obtain the signals, it is better in many cases for T2 to be long, but there are also many cases where, even if T2 is short, it suffices if the signals are obtained, by an appropriate signal obtaining technique, for instance immediately after the excitation thereof.
Typically, T1 of the gray matter of the brain of the human body is 1.0 when it is measured in a magnetic field of 1T. Further, typically, T2 of the gray matter of the human brain is 0.1. It has been conventionally believed that there is no method or means for changing these relaxation times T1 and T2 in a given static magnetic field (of 1.0 T, 1.5 T or the like) and at a given temperature (substantially 37xc2x0 C. of the human body) unless some chemical substance or the like is introduced into the human body.
More specifically, it is known that the ions of a magnetic material such as a transition metal and lanthanide ions have unpaired electronic spins which have magnetic moments several hundreds of times as large as protons, and thus have strong relaxation effects. As an application example of such substances, the injection of a gadolinium compound, which is a paramagnetic material, into the circulatory system of an examination subject is widely practiced in the field of clinical MRI. If a gadolinium compound is introduced into the tissue of a living body, it has a relatively larger shortening effect on T1, which is originally long, than on T2 which is originally short.
In other words, if the gadolinium compound is introduced into a vein, then it is absorbed into the blood or the brain tissue or the like if the cerebral blood vessel barrier has been destroyed by a cerebral infarction or the like. This selectively shortens the T1 of the tissue, so that the site of disease or the like can be selectively imaged or depicted in a T1-weighted image (that is, an image which is generated, by obtaining successive sets of magnetic resonance signals by repeating the excitation after each return of the spins to the initial state.) In such an image a substance which has a short T1 and is therefore apt to return to the initial state in which, even if previously excited, it can be excited again, produces a higher amplitude signal and thus appears brighter in the image.
A T2-weighted image is generated from a signal that is not obtained immediately after the excitation, but is obtained as a dark signal after waiting for a substance with a shorter T2 to become irregular and non-uniform in phase by the T2 relaxation and become undetectable.
Further, in the middle 1960""s, E. O. Stejskal and J. E. Tanner developed a diffusion measurement method by nuclear magnetic resonance that uses a motion probing gradient (MPG) pulses. [E. O. Stejskal and J. E. Tanner, xe2x80x9cSpin diffusion measurements: spin-echoes in the presence of time-dependent field gradient.xe2x80x9d J. Chem. Phys. Vol. 42: pp. 288-292, published in 1965].
This is a method of measuring the magnitude of the movement of spins as a diffusion coefficient by utilizing the fact that, as long as the spins perform a precession at a stationary position, no influence is exerted even if two gradient magnetic fields which are identical in magnitude but opposite in direction are successively applied as MPG pulses, but, if the spins are moved by the diffusion, then the phases are made irregular and non-uniform eventually by the application of the MPG pulses. The MPG pulses may be applied by making them identical with each other in magnitude and direction and putting 180xc2x0 RF pulses between them.
Further, D. Le Bihan, etc. introduced MRI techniques that incorporate MPG pulses into imaging sequences of MRI in mid-1980s. [D. Le Bihan, E. Breton, D. Lallemand, P. Granier, E. Cabanis and M. Laval-Jeantet, xe2x80x9cMR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurological disorders.xe2x80x9d Radiology Vol. 161: pp. 401-407, published in 1986].
Since then, the diffusion-weighted MRI techniques have been widely used as a very important imaging methods because, for important lesions like acute cerebral infarctions which cannot be depicted, unless two or three days lapse after the beginning of the disease, by T1-weighted imaging or T2-weighted imaging. Using diffusion-weighted imaging, these important lesions are imaged 20 to 30 minutes after the development of the disease.
The diffusion of certain molecules in the same substance, such as water molecules diffusing in water, is called self-diffusion. Accordingly, the diffusion coefficient of a substance itself refers to the self-diffusion coefficient. Self-diffusion is originally isotropic. However, among the movements of spins in living bodies, etc., not only do movements due to diffusion occur, but also some movements due to blood flow occur. More precisely, therefore, the measured diffusion coefficient of the water molecules is called the apparent diffusion coefficient (ADC). In particular, if the gradient factor attenuation value (which is sometimes abbreviated b-factor) that is determined dependent on the magnitude, the length in time and the pulse interval of each of the MPG pulses) is very small, the detection of only the movement due to the diffusion of the spins is very difficult, because the movement of the spins due to the blood flow, etc. also is detected. However, MPG pulses of such a degree that are in practical use in ordinary diffusion-weighted imaging sequences in clinical MRI, etc. at present can make the ADC value almost equal to the diffusion coefficient by sufficiently increasing the b-factor. Concerning the b-factor, details are given in the above-mentioned literature of Le Bihan, etc.
Further, a method of making a measurement by magnetic resonance while flowing an electric current through an electrolyte solution, is disclosed in U.S. Pat. No. 5,757,185.
The aforementioned patent states that by flowing an electric current, changing with time, the motion of the ions or molecules caused only by the electric current can be detected by nuclear resonance, with respect to the direction in which the gradient magnetic field is applied. Motion caused by diffusion is not detected.
There is no discussion in the aforementioned patent that applying an electric current through an electrolyte solution has any effect on T1 or T2. Moreover, the technique according to the aforementioned patent for detecting the motion of the ions or molecules produced by an electric field and thus differs from known techniques for detecting the self-diffusion that develops isotropically.
It is an object of the present invention to provide a technique for markedly shortening T1 or T2 of a water-containing substance such as an electrolyte solution, the tissues of a living body or human tissues without using an intravenous injection or the like of a paramagnetic material such as a gadolinium compound or the like.
Another object of the present invention is to provide a technique for markedly increasing the ADC of a water-containing substance, so that the diffusion-weighted sensitivity is enhanced, in the context of a diffusion-weighted MRI or diffusion-weighted MRS.
Still another object of the present invention is to provide a technique for measuring the spatial distribution of the electrical properties of a water-containing substance by the use of MRI or MRS.
Still another object of the present invention is to provide a technique for measuring the spatial distribution of the electric currents in the interior of a water-containing substance by the use of MRI or MRS.
The first object is achieved in accordance with the present invention wherein, by applying an electric current through a water-containing substance, T1 or T2 of the substance is reduced.
The first object also is achieved in accordance with the present invention in a method for obtaining magnetic resonance images or spectra wherein a water-containing substance is placed in a static magnetic field, and, by a radio-frequency magnetic field, nuclear spins in the substance are excited to generate magnetic resonance signals, and wherein, by applying an electric current through said substance, the T1 or T2 of the substance is reduced.
The second object is achieved in accordance with the present invention wherein by applying an electric current through a water-containing substance, the apparent diffusion coefficient (ADC) of the substance is increased.
The second object also is achieved in accordance with the present invention also lies in a method for obtaining a magnetic resonance image or spectrum wherein a water-containing substance is placed in a homogeneous static magnetic field, and, by a radio-frequency magnetic field, nuclear spins in the substance are excited to generate magnetic resonance signals, and wherein, by applying an electric current through the substance, the ADC of the substance is increased.
The third and fourth objects are achieved in accordance with the present invention in a method for obtaining a magnetic resonance image or spatial information representing an electrical property of a water-containing substance wherein a T1-weighted, T2-weighted or diffusion-weighted magnetic resonance image, or localized magnetic resonance spectra is/are obtained,while applying an electric current through the substance, and wherein these images or spectra are compared to images or localized spectra obtained without applying the electric current.
The water-containing substance can be an electrolyte solution or the tissues of a living body.
The first object also is achieved in accordance with the present invention in an apparatus for obtaining a magnetic resonance image of a water-containing substance having a basic field magnet which generates a homogeneous static magnetic field, an RF system which generates a radio-frequency field, a gradient system which generates gradient magnetic fields, and a computer which generates an image from the received magnetic resonance signals and an arrangement for applying an electric current through the substance while the nuclear spins are processing, to reduce T1 or T2 of the substance.
A further embodiment of the present invention is an apparatus for obtaining a magnetic resonance image of a water-containing substance having a basic field magnet which generates a homogeneous static magnetic field, an RF system which generates a radio-frequency magnetic field, a gradient system which generates gradient magnetic fields, and a computer which generates an image from the received magnetic resonance signals, and an arrangement for applying motion probing gradient (MPG) pulses through the substance, and an arrangement for applying an electric current through the substance, to increase the ADC of the substance as the magnetic resonance signals are being generated and received.
A further embodiment of the present invention is a method for obtaining spatial information, by magnetic resonance, representing the internal electric current evoked in a water-containing substance, wherein T1-weighted or T2-weighted or diffusion-weighted magnetic resonance images or localized magnetic resonance spectra while an internal current is caused to flow in the substance, and wherein images or localized spectra are obtained without an internal current flowing in the substance, which are compared to the images or the localized spectra obtained with the internal current.
Even if the internal current is evoked in the tissue of a living body instead of being externally applied, the present invention can be practiced. In particular, even if the electric current in the tissue of a living body is evoked by an external stimulus to the living body tissues or by the internal brain activity in the living body, the present invention can be practiced.
The main cause for the relaxation phenomenon of the spins excited in water lies in the dipole-dipole interaction. One water molecule has two protons. Each rotates with a positive charge, as a result of which a magnetic field is emitted as a magnetic dipole having an N pole and an S pole. Moreover, the individual protons are each disposed within the magnetic fields emitted by surrounding protons. Further, each water molecule is experiencing thermodynamic molecular motion (Brownian motion). The correlation time (i.e., the time constant when the state at a certain instant is lost by the thermodynamic molecular motion, which becomes shorter as the thermodynamic molecular motion increases of the thermodynamic molecular motion of water existing as a liquid is much shorter than the cyclical period of the spin precession.
If the correlation time of the thermodynamic molecular motion reaches the same order as that of the cyclical period of the spin precession, many protons are subjected to radio-frequency magnetic fields generated by the other protons, on the same order as that of the precessions, and accordingly on the same order as the resonance frequencies but having various frequencies on the same order as the precessions, and accordingly on the same order as that of the resonance frequencies, but the protons exhibit various frequencies, like white noise. Then, the spins excited by the radio-frequency magnetic fields with a single resonant frequency from the outside cannot keep the excitation state any longer and thus become relaxed. This is the T1 relaxation caused by the dipole-dipole interaction.
Further, if the correlation time of the thermodynamic molecular motion becomes very long, then one proton also is disposed in a static magnetic field produced by the magnetic fields emitted from the other protons, so that the precession which would otherwise occur at a cyclical period due to the constant external magnetic field, is disturbed by the existence of many surrounding protons, and thus becomes irregular and non-uniform. This is the T2 relaxation caused by the dipole-dipole interaction.
On the other hand, one water molecule has two protons which have positive charges and one oxygen nucleus which has a negative charge, bonded at an angle of about 105xc2x0, and therefore, the molecule itself is a weak electric dipole. For example, in saline solution, sodium and chlorine exist in an ionized state, and the electric dipoles of the water molecule are attracted or repulsed by the dissociated ions, forming, around the individual electrolytic ions, many semi-stable structures, called hydration shells, containing many water molecules. Semi-stability refers to the state in which the total number of the electric dipoles does not change significantly with time, but replacement of the dipoles by surrounding dipoles is constantly taking place. Also in human body tissue, sodium ions of about 150 mM exist in the extracellular fluid and potassium ions of about 150 mM exist in the intracellular fluid, so that, around these ions, hydration shells are formed.
When an electric current is applied, the electrolytic ions move together with the hydration shells in a manner taking many water molecules with them. It is believed that, in this case, the thermodynamic molecular motion of the water molecules is restricted by the movement of the electrolytic ions, so that the correlation time is changed. As a result, the above-mentioned T1 relaxation and T2 relaxation based on the above-mentioned dipole-dipole interaction are caused, and T1 and T2 become markedly shorter.
Further, it is believed that, if an electric current is applied, the electrolytic ions move with the hydration shells in a manner taking many water molecules with them, as a result of which the movement of the water molecules is caused, and thus the ADC is remarkably increased. Here, the important feature pertaining to the increase of the ADC in the present invention is that the increase is developed isotropically. The mechanism therefor is believed to be in that the replacement, in a direction perpendicular to the movement, of the water molecules with the surrounding water molecules, which is caused by the movement of the hydration shells, occurs isotropically. Therefore, it is believed that the increase of the ADC in the present invention is also due to the fact that the diffusion coefficient substantially increases.
Further, T1-weighted or T2-weighted images or diffusion-weighted images can be obtained while applying an electric current through a water-containing substance, and a comparison is made between these images and corresponding control images obtained without applying an electric current. Such a comparison can be subtraction or division of attributes the images, or image calculations such as statistical inspection, etc. among many images. The tissues through which the electric current flow is higher exhibit a greater T1 shortening effect or T2 shortening effect or ADC increasing effect according to the present invention. Therefore, images in which the distribution of the electrical conductivity is represented can be obtained.
Further, according to the present invention, T1-weighted images can be obtained while applying an electric current through a water-containing substance, then T1 is shortened, as a result of which the intensity of the signals obtained is markedly high, and therefore the obtained images are bright. Alternatively, a T1-weighted image can be obtained with a xe2x80x9cconventionalxe2x80x9d brightness but the scan can be completed in a shorter time as a whole in connection with MRI or MRS. Accordingly, in a clinical MRI apparatus, the stores the patients can be markedly reduced and patient throughput can be increased.
Further, according to the present invention, diffusion-weighted images can be obtained, while applying an electric current through a water-containing substance, causing the ADC to be markedly increased, as a result of which images in which the contrast of the signals obtained is markedly strong are obtained.
The present invention is based on the finding that, when an electric current exists in a water-containing substance, T1 or T2 is shortened, or ADC is increased. The electric current which yields such effects need not be applied from outside the subject, but can be evoked internally, such as in the case of the water-containing substance being tissue in a living body, such as brain tissue.
More specifically, the brain evokes an electric current internally in response to an external stimulus or by internal brain activity. In a living body, the nerve tissues of the brain or the like are relatively easy to supply with an electric current, and as a result of the application of the electric current, a natural biomagnetic field is generated. The intensity of such electric fields emitted in the surrounding electrolyte, however, is small. Further, the duration of the electrical activities is very short in many cases.
Thus, T1-weighted or T2-weighted or diffusion-weighted magnetic resonance images or local magnetic resonance spectra are obtained when an internal electric current exists and when no internal electric current exists, and, between the data obtained when the internal electric current exists and the data obtained when no internal electric current exists, a comparison is made by performing subtractions and divisions or, among many datasets, a comparison is made by performing statistical inspection, etc. This allows information pertaining the spatial distribution of the internal currents and/or magnetic resonance images which represent the spatial distribution of the internal currents to be obtained.